Itgb1-KO Mouse

Itgb1, also known as Integrin beta1, is a member of the integrin superfamily. Integrins are involved in cell adhesion, tissue repair, immune response, and tumor metastasis. Itgb1 promotes cell adhesion and growth, and is widely expressed in epithelial cells. It is associated with multiple signaling pathways, such as the Wnt/β -catenin, NF -κB, and mTORC2/AKT pathways, which are crucial for various biological processes [5,2,7].

In non-small cell lung cancer (NSCLC), knockdown of Itgb1 reduces clonogenic survival, cell viability, and induces apoptosis post-irradiation. It also enhances radiation-induced DNA damage and G2/M phase arrest, and suppresses epithelial-mesenchymal transition (EMT) by inhibiting the expression and intracellular translocation of YAP1, suggesting that Itgb1 may be a target to overcome NSCLC radioresistance [1]. In ovarian cancer, ALKBH5-mediated m6A demethylation of Itgb1 mRNA increases Itgb1 expression, activates FAK signaling, and enhances tumor-associated lymphangiogenesis and lymph node metastasis [3]. In gastric cancer, high Itgb1 expression is correlated with deep invasion, advanced clinical stage, poor prognosis, and immune suppression, and may be a potential predictor of immunotherapy efficacy [5]. In esophageal adenocarcinoma, high Itgb1 expression is associated with lymph node metastasis and impaired overall survival, especially in patients without prior neoadjuvant therapy [6]. In diffuse gastric cancer, high Itgb1 expression is related to worse prognosis, and is involved in cell adhesion, proliferation, metabolism reprogramming, and immune regulation [8]. In osteosarcoma, ZCCHC4 promotes tumor progression by upregulating Itgb1 [9].

In conclusion, Itgb1 plays a significant role in multiple diseases, especially in cancer. Studies on Itgb1 using gene-knockout or knockdown models have revealed its functions in tumor radioresistance, chemoresistance, metastasis, and immune regulation, providing potential therapeutic targets for these diseases. It is also involved in non-cancerous conditions like osteoarthritis, where it alleviates the disease by activating the cAMP pathway [4].

References:

1. Li, Yuexian, Sun, Cheng, Tan, Yonggang, Li, Yuchao, Zou, Huawei. 2021. ITGB1 enhances the Radioresistance of human Non-small Cell Lung Cancer Cells by modulating the DNA damage response and YAP1-induced Epithelial-mesenchymal Transition. In International journal of biological sciences, 17, 635-650. doi:10.7150/ijbs.52319. https://pubmed.ncbi.nlm.nih.gov/33613118/

2. Li, Jianjun, Xiao, Xuechun, Ou, Yang, Yang, Guang, Yang, Shuang. 2023. USP51/PD-L1/ITGB1-deployed juxtacrine interaction plays a cell-intrinsic role in promoting chemoresistant phenotypes in non-small cell lung cancer. In Cancer communications (London, England), 43, 765-787. doi:10.1002/cac2.12460. https://pubmed.ncbi.nlm.nih.gov/37386737/

3. Sun, Rui, Yuan, Lin, Jiang, Yi, Zhang, Lin, Cheng, Wenjun. 2023. ALKBH5 activates FAK signaling through m6A demethylation in ITGB1 mRNA and enhances tumor-associated lymphangiogenesis and lymph node metastasis in ovarian cancer. In Theranostics, 13, 833-848. doi:10.7150/thno.77441. https://pubmed.ncbi.nlm.nih.gov/36632222/

4. Xie, Lifeng, Li, Zhengnan, Chen, Zhijun, Li, Mingzhang, Tao, Jun. 2023. ITGB1 alleviates osteoarthritis by inhibiting cartilage inflammation and apoptosis via activating cAMP pathway. In Journal of orthopaedic surgery and research, 18, 849. doi:10.1186/s13018-023-04342-y. https://pubmed.ncbi.nlm.nih.gov/37941009/

5. Gu, Wenchao, Sun, Hui, Zhang, Meng, Sheng, Weiqi, Wang, Lei. 2022. ITGB1 as a prognostic biomarker correlated with immune suppression in gastric cancer. In Cancer medicine, 12, 1520-1531. doi:10.1002/cam4.5042. https://pubmed.ncbi.nlm.nih.gov/35864742/

6. Damanakis, Alexander I, Wahler, Isabell, Fuchs, Hans, Quaas, Alexander, Gebauer, Florian. 2022. Integrin beta1 (ITGB1) as a prognostic marker in esophageal adenocarcinoma. In Scientific reports, 12, 20745. doi:10.1038/s41598-022-25071-y. https://pubmed.ncbi.nlm.nih.gov/36456612/

7. Zhou, Weiwei, Liu, Weizhe, Zhou, Dingyan, Li, Aiying. . ITGB1 Suppresses Autophagy Through Inhibiting The mTORC2/AKT Signaling Pathway In H9C2 Cells. In Die Pharmazie, 77, 137-140. doi:10.1691/ph.2022.2351. https://pubmed.ncbi.nlm.nih.gov/35655382/

8. Zhu, Xingyu, Chen, Hao, Li, Han, Shang, Liang, Li, Leping. 2023. ITGB1-mediated molecular landscape and cuproptosis phenotype induced the worse prognosis in diffuse gastric cancer. In Frontiers in oncology, 13, 1115510. doi:10.3389/fonc.2023.1115510. https://pubmed.ncbi.nlm.nih.gov/37007126/

9. Luo, Lingli, Tang, Xiaojun, Liu, Linghua, Chang, Guiping, Xiao, Zhihong. . ZCCHC4 Promotes Osteosarcoma Progression by Upregulating ITGB1. In Critical reviews in eukaryotic gene expression, 33, 31-39. doi:10.1615/CritRevEukaryotGeneExpr.2023047798. https://pubmed.ncbi.nlm.nih.gov/37606162/